By E. Roland. Texas A&M University, Kingsville. 2018.

No epi- demiological studies of this antihypertensive agent in pregnant women have been pub- lished cheap vasodilan 20 mg with amex blood pressure medication used to treat anxiety. There were no malformations among 22 infants born to mothers who received captopril during the first trimester (Kreft-Jais and Boutroy buy cheap vasodilan 20mg on-line blood pressure chart stroke, 1988), but no controlled stud- ies have addressed whether or not captopril is a potent human teratogen. Of 29 infants with neonatal renal failure, nine were born to women who had used captopril throughout pregnancy (Rosa and Bosco, 1991). These antihypertensives are, therefore, contraindicated for use during pregnancy, and should be avoided if possible. No animal teratology studies have been published for captopril, but an increased frequency of fetal deaths was reported in two animal studies (Pipkin et al. Of 29 cases of perinatal renal failure, 18 occurred follow- ing maternal therapy with enalapril during pregnancy (Rosa and Bosco, 1991). Among 29 infants with neonatal renal failure, two were born to women who used lisinopril during pregnancy (Rosa and Bosco, 1991). The risk of congen- ital anomalies following use during the first trimester is unknown, but use during the Special considerations 69 second and third trimesters is associated with a significant risk of fetal-neonatal compli- cations. The complications include: oligohydramnios, fetal/neonatal renal failure, and decreased calcification of the cranium (Friedman and Polifka, 2006). Cardiac arrhythmias Fortunately, life-threatening cardiac arrhythmias are uncommon during pregnancy. However, certain less serious arrhythmias may actually be increased in frequency during pregnancy (Brown and Wendel, 1989). Paroxysomal supraventricular tachycardia Paroxysmal supraventricular tachycardia occurs among 1–2 per 500 young women, and frequently occurs in those without overt heart disease (Brown and Wendel, 1989). Pregnancy may increase risk for this type of arrhythmia (Meller and Goldman, 1982; Szekely and Snaith, 1953). If vagal stim- ulation is unsuccessful, verapamil at 5–10 mg intravenously will prove successful in most cases in pregnant women. Recently adenosine, in a dose of 6 mg given as a rapid intravenous bolus, has been recommended for the treatment of supraventricular tachycardia. As previously mentioned, there is little information regarding the safety of this agent during pregnancy. However, there are several reports regarding its efficacy in pregnant women (Afridi et al. Electrical cardioversion should be reserved for patients with cardiac decompensation in whom medical therapy has failed. Patients with frequent recurrences of this arrhythmia can usually be treated with dig- italis and/or verapamil, quinidine, and propranolol as needed (Brown and Wendel, 1989; Zipes, 1988). Atrial fibrillation Atrial fibrillation is uncommon in pregnant women, and this event points to underlying cardiac or thyroid disease. Mitral valve disease, secondary to rheumatic heart disease, is the most commonly encountered underlying cause of atrial fibrillation in the pregnant patient. Chronic atrial fibrillation treatment is generally directed at slowing the ventric- ular rate through medical therapy, with such medications as digitalis, with or without verapamil or propranolol (Brown and Wendel, 1989). Electrical cardioversion is indicated for significant cardiac decompensation and has been utilized in pregnant women without apparent adverse effects (Schroeder and Harrison, 1971). Ventricular tachycardia is a life-threatening arrhythmia as it may lead to ventricular fibrillation, cardiac decompensation, and death. Fortunately, this arrhythmia is rarely encountered during pregnancy, especially in the absence of specific cardiac disease such as myocardial infarction. Therapy consists primarily of electric cardioversion, especially if the patient is hemodynamically unstable. Lidocaine, pro- cainamide, or bretylium may be used to prevent recurrence of tachycardia. Treatment is primarily electrical cardioversion followed by lidocaine or bretylium to prevent further fibrillation. Special considerations 71 Hypertension Hypertension is one of the most common medical complications encountered during pregnancy and presents as chronic hypertension, pregnancy-induced hypertension, or preeclampsia.

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Nalbuphine is superior to codeine as an analgesic order vasodilan 20mg fast delivery blood pressure in children, and any vasodilation that results would probably decrease blood loss discount 20mg vasodilan with mastercard arteriographic embolization. Muscarinic receptor antagonists such as benztropine, trihexyphenidyl, and diphenhydramine are used to manage the reversible extrapyramidal dysfunction (e. Lithium causes goiter in a significant number of patients; however, thyroid dys- function does not occur in all such patients, and when it does it presents as hypothyroidism (not hyper-T), High-Na diets increase lithium elimination; low Na increases lithium plasma levels. Uncoupling of vasopressin receptors is characteristic of lithium, leading to a nephro- genic diabetes insipidus. Although potential teratogenicity is a concern during pregnancy, lithium does not cause neural tube defects but may cause abnormalities in heart valves. Lithium takes 10 to 20 days for effectiveness, and in acute mania it is often necessary to calm the patient with parenteral antipsychotic drugs such as fluphenazine or haloperidol. Disulfiram (Antabuse) is an inhibitor of aldehyde dehydrogenase used in some alcohol rehabilitation programs, and naltrexone (an opioid antagonist) is approved for use in alcoholism because it decreases "craving. Muscarinic receptor blockers may improve muscle rigidity and tremor in Parkinson disease but result in very little improvement in bradykinesia; thus, they are mainly considered as adjunctive to the use of drugs that improve dopaminergic function. Symptoms of bipolar disorder, particularly those related to the manic phase, can be suppressed by several drugs that are commonly used for seizure disorders. Some of these drugs are teratogenic, including carbamazepine, phenytoin, and valproic acid, and are contraindicated in pregnancy. Methylphenidate is used in attention deficit disorder and has not been shown to have value in bipolar disorder. Recently, the anticonvulsant gabapentin has been shown to be effective in bipolar disorders. The drug has no abuse liability and will not suppress withdrawal symptoms in patients who have become physically dependent on barbiturates, benzodiazepines, or ethanol. Bupropion is an antidepressant, also approved for management of dependence on nicotine. Thioridazine is distinctive because it is the only phenothiazine that has signifi- cant cardiotoxic potential. Drugs that accentuate this by inhibiting the repolarizing K current (phase 3), which include thioridazine and the tricyclic antidepressants, are likely to have enhanced cardiotoxic potential in such patients. The signs and symptoms described are typical of withdrawal from physi- cal dependency on an opioid that has efficacy equivalent to a full agonist-in this case, meperidine. Orthostatic hypotension occurs with both tricyclic antidepressants and phe- nothiazines because both types of drug can block alpha-adrenergic receptors in venous beds. Their ability to block M receptors leads to xerostomia (not salivation) and mydriasis (not miosis). Tricyclics and phenothiazines also share a common tendency to decrease seizure threshold and cause weight gain (not loss). Carbamazepine and the local anesthetic procaine block axonal Na channels; ethosuximide may block Ca channels in thalamic neurons. Fentanyl is a full agonist at opioid receptors and provides analgesia in cancer pain equivalent to morphine, so there is no good reason to have morphine on hand, and it would be a danger to the patient in terms of accidental overdose. Apomorphine is an <, emetic, hardly appropriate given the stimulatory effects of opioids on the emetic center. Likewise, loperamide is used in diarrheal states, and patients on strong opioids are almost certain to be constipated; for this reason, a stool softener like docusate should be available to the patient. Mechanismw______ of Action,______ of Antimicrobial Agents Mechanism of Action Antimicrobial Agents Inhibition of bacterial cell-wall synthesis Penicillins. Mechanisms of Resistance to Antimicrobial Agents Antimicrobial Agents Primary Mechanism( s) of Resistance Penicillins and cephalosporins Production of beta-lactamases, which cleave the beta- lactam ring structure; change in penicillin-binding proteins; change in porins Aminoglycosides (gentamicin, Formation of enzymes that inactivate drugs streptomycin, amikacin, etc. Urticarial skin and maculopapular rashes, rash common, but severe reactions, including anaphylaxis, are possible. Enterococci o Renal clearance similar to penicillins, with active tubular secretion blocked by probenecid o Dose modification in renal dysfunction o Cefoperazone and ceftriaxone are largely eliminated in the bile Side effects: o Hypersensitivity: Incidence: 2% Wide range, but rashes and drug fever most common Positive Coombs test, but rarely hemolysis Assume complete cross-allergenicity between individual cephalosporins and partial cross-allergenicity with penicillins (about 5%) Most authorities recommend avoiding cephalosporins in patients allergicto penicillins (for gram-positive organisms, consider macrolides; for gram-negative rods, consider aztreonam) o Other: Disulfiram-like effect: cefotetan, cefoperazone, and cefamandole Hypoprothrombinemia 184 me&ical Antibacterial Agents Imipenem and Meropenem Mechanism of action: - Same as penicillins and cephalosporins - Resistant to beta-lactamases Spectrum: - Gram-positive cocci, gram-negative rods (e.

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Before doing so the epileptogenesis of absence seizures (petit mal) justifies separate consideration order vasodilan 20 mg with visa blood pressure medication regimen. If its neurons are stimulated while slightly hyperpolarised they show repetitive burst discharges in rat brain slices followed by a marked after- hyperpolarisation vasodilan 20 mg without a prescription blood pressure drugs, i. In fact cloning studies in mutant mice strains with features of absence epilepsy show defects in the subunit structure of these channels (Fletcher et al. This may not mean that it does not occur but that the avid uptake mechanism for glutamate ensures that levels do not rise above basal, unless the stimulation is very extreme. This may explain why perfusates of the lateral ventricle, obtained during kindled seizures induced by the stimulation of the amygdala, showed elevated glutamate levels, but only after very intense neuronal disharges. Kindling induced by the intraventricular injection of folic acid in rats produced significant increases in cortical glutamate and aspartate, but only the latter correlated directly with increased spiking. With kindling induced by electrical stimulation of the frontal cortex the only change observed alongside the increase in after-discharge was a reduction in glutamine, although this could reflect its utilisation in providing the extra glutamate required for spiking and epileptic activity. In fact pyridoxal phosphate deficiency has been shown to be the cause of convulsions in children. These discharges have also been seen in the few humans on which the drugs have been tested unsuccessfully. The normal control pattern (phase a) quickly takes on an arousal state (phase b, 2±5 min). This gives way to waves of steadily increasing amplitude but low frequency (2 Hz) for 8±18 min (phase c) on which a few spikes gradually appear at 20 min (phase d). Spikes gradually predominate after some 26 min (phase e) until they group to give a full ictal seizure at 30 min (phase f). Records from the screw electrodes (a) showed the expected progressive change from wave-like (i) to spiking (ii) similar to phases c and d in Fig. Inhibition of glutamate release was thought to be the mode of action of lamotrigine. But it now seems likely that the actual block of sodium channels is its primary action (see later). Generally a reduction in monoamine function facilitates experimentally induced seizures (see Meldrum 1989) while increasing it reduces seizure susceptibility. The variability of the procedures used and results obtained do not justify more detailed analysis here. Some mention should perhaps be made of dopamine, considering its role in the control of motor function. How the drugs currently available for the treatment of epilepsy may utilise these mechanisms will now be considered. The decision on which drug to use depends not only on their proven efficacy in a particular type of epilepsy (some drugs are inactive in certain forms) but also what side-effects they have Ð many are sedative Ð how they interact with other drugs and how often they need to be taken. Compliance is a problem over a long period if dosing is required more than once a day. Only the latter have been developed chemically to modify the known synaptic function of the amino acids. It was largely replaced in 1932 by phenytoin for the management of tonic±clonic seizures and partial and secondary epilepsy. These remained, apart from the introduction of the benzodiazepines, the mainstay of therapy until the last decade. They were introduced solely on their ability to control experimentally induced seizures. Studies in cultured spinal cord neurons (Macdonald and McLean 1986) have shown that concentrations of phenytoin equivalent to those occurring clinically do not affect the resting membrane potential or the shape of a single-action potential but reduce the rapid discharge induced by depolarising the neuron, while leaving the first action potential intact (Fig. It is believed to block voltage-dependent sodium channels (not those mediating the synaptic currents) after their activation, i. Currently there are no clinically useful drugs that act as glutamate receptor antagonists seizures and clinically in focal and generalised epilepsy. Also, since they act only on the inactivated channel, they will not affect normal neuronal function, which is why in the experimental study, the first action potential remains unaltered. Neither compound is of any value against absence seizures and may exacerbate them.

Only 21 pregnancies with early exposure to the monoamine oxidase inhibitors have been published 20mg vasodilan with visa arteria umbilical, and there was an apparent increase in malformations associated with the use of these agents (Heinonen et al buy vasodilan 20 mg without prescription blood pressure medication used for sleep. However, it is impossible to draw clinically useful information from such data because the sample size is too small. Animal teratology studies undertaken with with monoamine oxidase inhibitors are not consistent, with some reporting no increase in the frequency of birth defects with tranylcypromine (Poulson and Robson, 1963), while others reported an increase in both the mortality rate and stillbirth rate in the isocarboxazid group (Werboff et al. An increase in placental infarcts occurred in pregnant rats who received iproniazid dur- ing gestation (Poulson et al. Decreased fertility was reported in the offspring of rats treated with nialamide (Tuchmann-Duplessis and Mercier-Parot, 1963). No animal teratology studies have been published on the monoamine oxidase inhibitor, phenelzine. These agents are generally not used during pregnancy because of potential adverse maternal side effects, and are category C drugs. Failure to do so may result in hypertensive crisis (Yonkers and Cunningham, 1993). Importantly, monoamine oxidase inhibitors given with meperidine, or other similar agents, may cause hyperthermia (Yonkers and Cunningham, 1993). These drugs are continued only as long as the underlying cause of psychosis is present because 190 Psychotropic use during pregnancy of the tardive dyskinesia associated with these medications. Commonly used antipsychotics or neuroleptic agents, with the exception of clozapine (Box 10. These agents have numerous side effects including anticholinergic effects such as constipation, dryness, and orthostatic hypotension, and extrapyramidal side effects such as akathisia (Miller, 1996; Yonkers and Cunningham, 1993). Antipsychotics may cause transient neonatal side effects including withdrawal symp- toms and extrapyramidal dysfunction (hand posturing, tremors, and irritability) (Auerbach et al. Two major confounders make it problematic to evaluate possible associations of antipsychotics and congenital malformations. First, many of these agents are used for indications other than psychosis (hyperemesis, anxiety) where lower doses may be used (Yonkers and Cunningham, 1993). Second, the psychiatric disease itself may be associ- ated with an increased frequency of malformations (Elia et al. It has pharmacological properties similar to the piperazine phenothiazines, although it is not chemically related to them. Haloperidol is used as a major tranquilizer to treat psychosis, Tourette’s syndrome, mania, and severe hyperactivity. In a cohort study of 98 pregnant women who received haloperidol for hyperemesis gravi- darum (90 during early pregnancy), there were no obvious congenital anomalies or adverse fetal effects noted (van Waes and van de Velde, 1969). Among 56 infants whose mothers took haloperidol during the first trimester, the frequency of congenital anomalies was not increased (3, or 5. Two cases of newborns with limb reduction malformations after haloperidol exposure during the first trimester have been published (Dieulangard et al. The pertinence of animal studies to the clinical use of haloperidol in human pregnancy is unclear. No information on the use of this tricyclic antipsychotic during pregnancy in humans has been pub- lished. In mice and rats whose mothers were treated with loxapine during embryogene- sis, a low incidence of exencephaly and an increase in fetal loss was observed in only one mouse litter out of 20 studied (Mineshita et al. Phenothiazines Phenothiazines are related drugs with potent adrenergic-blocking action. Pharmacologic effects include central nervous system depression, prolonged effects of narcotic or hyp- notic drugs, and hypotensive, antiemetic and antispasmodic activity. Two well- described side effects – hypotension and extrapyramidal tract symptoms – of this drug need special attention. The frequency of congenital anomalies was not increased among 140 infants born to women exposed to this agent during the first trimester of pregnancy (Heinonen et al. In a cohort study of 264 pregnant women who took chlorpro- mazine for hyperemesis gravidarum in the first trimester, the frequency of congenital anomalies was not increased (Farkas and Farkas, 1971). One study reported an increase in the frequency of congenital anomalies in offspring exposed to chlorpromazine com- pared to controls (Rumeau-Rouquette et al. The frequency of congenital anomalies or pregnancy loss in 52 pregnancies was not increased among those exposed to chlorpromazine.

Premature labour: Gluc 5% should be used to prepare the infusion to #risk of maternal pulmonary oedema generic vasodilan 20 mg without prescription arrhythmia login facebook. More than 10 micrograms/minute is rarely required; 20 micrograms/minute should not be exceeded discount vasodilan 20mg line arteria fibularis. Dose in renal impairment: adjusted according to creatinine clearance:1 * CrCl >20--50mL/minute: reduce the parenteral dose by 50%. Terbutaline sulfate | 805 Continuous intravenous infusion via a syringe pump Preparation of a 100 micrograms/mL solution (other strengths may be used according to local policies) 1. Inspect visually for particulate matter or discolor- ation prior to administration and discard if present. Continuous intravenous infusion (large volume infusion) Preparation of a 5 micrograms/mL solution (other strengths may be used according to local policies) 1. Inspect visually for particulate matter or discolor- ation prior to administration and discard if present. Inspect visually for particulate matter or discolor- ation prior to administration and discard if present. Technical information Incompatible with No information Compatible with Flush: NaCl 0. Stability after From a microbiological point of view, should be used immediately; however, prepared preparation infusions may be stored at 2--8 C and infused (at room temperature) within 24 hours. Additional information Common and serious Immediate: Hypersensitivity reactions have been reported. Action in case of The preferred antidote is a cardioselective beta-blocker, but use with caution in overdose patients with a history of bronchospasm. This assessment is based on the full range of preparation and administration options described in the monograph. Teriparatide | 807 Teriparatide 250 micrograms/mL solution in 3-mL pre-filled multidose pen (28 doses) * Teriparatide is a recombinant fragment of human parathyroid hormone. Pre-treatment checks * Avoid in pre-existing "Ca, severe renal impairment, metabolic bone diseases including hyperpara- thyroidism and Paget disease, skeletal malignancies or bone metastases or previous radiation therapy to the skeleton. Dose in renal impairment: no dose adjustment required in mild impairment; use with caution in moderate impairment; do not give in severe renal impairment. Technical information Incompatible with Not relevant Compatible with Not relevant pH Not relevant Sodium content Negligible Excipients Contains metacresol (may cause hypersensitivity reactions). In use: Once opened, the pen should be used for a maximum of 28 days and then discarded. Urinary calcium Periodically * In patients with suspected active urolithiasis or pre-existing hypercalciuria. Additional information Common and serious Immediate: Hypersensitivity reactions: acute dyspnoea, facial oedema, undesirable effects generalised urticaria, chest pain, oedema (mainly peripheral). Antidote: No known antidote; stop administration and give supportive therapy as appropriate. This assessment is based on the full range of preparation and administration options described in the monograph. Terlipressin | 809 Terlipressin 1-mg dry powder vial with 5mL solvent 120 micrograms/mL (1mg/8. Pre-treatment checks Caution in patients with hypertension, atherosclerosis, cardiac dysrhythmias or coronary insufficiency. Hepatorenal syndrome (unlicensed): 1mg every 4--12 hours for 7--15 days appeared to improve renal function. Inspect visually for particulate matter or discolor- ation prior to administration and discard if present. Technical information Incompatible with No information Compatible with Flush: NaCl 0. Displacement value Negligible Stability after Use reconstituted vials immediately. Fluid balance * Terlipressin has approximately 3% of the antidiuretic effect of vasopressin and could cause fluid retention and #Na. This assessment is based on the full range of preparation and administration options described in the monograph.

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Still buy 20mg vasodilan overnight delivery blood pressure of 90 60, it is possible to analyze the circulatory system with reasonable accuracy using the concepts developed for simple fluids flowing in rigid pipes buy vasodilan 20mg line heart attack kid. The blood in the circulatory system brings oxygen, nutrients, and various other vital substances to the cells and removes the metabolic waste products from the cells. The blood is pumped through the circulatory system by the heart, and it leaves the heart through vessels called arteries and returns to it through veins. The mammalian heart consists of two independent pumps, each made of two chambers called the atrium and the ventricle. The entrances to and exits from these chambers are controlled by valves that are arranged to maintain the flow of blood in the proper direction. Blood from all parts of the body except the lungs enters the right atrium, which contracts and forces the blood into the right ventricle. The ventricle then contracts and drives the blood through the pulmonary artery into the lungs. In its passage through the lungs, the blood releases carbon dioxide and absorbs oxygen. The contraction of the left atrium forces the blood into the left ventricle, which on contraction drives the oxygen-rich blood through the aorta into the arteries that lead to all parts of the body except the lungs. Thus, the right side of the heart pumps the blood through the lungs, and the left side pumps it through the rest of the body. The large artery, called the aorta, which carries the oxygenated blood away from the left chamber of the heart, branches into smaller arteries, which lead to the various parts of the body. These in turn branch into still smaller arteries, the smallest of which are called arterioles. As we will explain later, the arte- rioles play an important role in regulating the blood flow to specific regions in Section 8. The arterioles branch further into narrow capillaries that are often barely wide enough to allow the passage of single blood cells. The capillaries are so profusely spread through the tissue that nearly all the cells in the body are close to a capillary. The exchange of gases, nutrients, and waste products between the blood and the surrounding tissue occurs by diffusion through the thin capillary walls (see Chapter 9). The capillaries join into tiny veins called venules, which in turn merge into larger and larger veins that lead the oxygen-depleted blood back to the right atrium of the heart. First the atria contract, forcing the blood into the ventricles; then the ventricles contract, forcing the blood out of the heart. Because of the pumping action of the heart, blood enters the arteries in spurts or pulses. The maximum pressure driving the blood at the peak of the pulse is called the systolic pressure. Ina young healthy individual the systolic pressure is about 120 torr (mm Hg) and the diastolic pressure is about 80 torr. As the blood flows through the circulatory system, its initial energy, pro- vided by the pumping action of the heart, is dissipated by two loss mecha- nisms: losses associated with the expansion and contraction of the arterial walls and viscous friction associated with the blood flow. Due to these energy losses, the initial pressure fluctuations are smoothed out as the blood flows away from the heart, and the average pressure drops. By the time the blood reaches the capillaries, the flow is smooth and the blood pressure is only about 30 torr. The pressure drops still lower in the veins and is close to zero just before returning to the heart. In this final stage of the flow, the movement of blood through the veins is aided by the contraction of muscles that squeeze the blood toward the heart. The radius of the aorta, for example, is about 1 cm; therefore, the pressure drop along the arteries is small. The rate of blood flow Q through the body depends on the level of physical activity. Of course, as the aorta branches, the size of the arteries decreases, result- ing in an increased resistance to flow. Although the blood flow in the nar- rower arteries is also reduced, the pressure drop is no longer negligible (see Exercise 8-2). The flow through the arterioles is accompanied by a much larger pressure drop, about 60 torr. Since the pressure drop in the main arteries is small, when the body is horizontal, the average arterial pressure is approximately constant throughout the body.

Since the majority of receptors are localized in cell membranes purchase vasodilan 20 mg on line arteria volaris indicis radialis, this sequence of events con- stitutes intercellular communication generic 20 mg vasodilan amex blood pressure medication first line. Another type of effector is the ion channel of an excitable membrane, which in its R (open) conformation allows the passage of about 10,000–20,000 ions in a single impulse, resulting in either membrane depolarization or polarization and a multitude of possible physiological phenomena. According to classical concepts, a recognition site is permanently associated with an effector site, and will regulate its operation on a one-to-one or some other stoichiometric basis. If this hypothesis is applied to the case of adenylate cyclase, one of two conditions would have to be assumed: that there are either as many adenylate cyclase isozymes as there are receptors acting through them, or that adenylate cyclase would need an enormous variety of specific recognition sites that can answer to many ligands. The mobile receptor concept is an attempt to offer a solution to this problem, in rec- ognizing that the lipid membrane is a two-dimensional liquid in which the embedded proteins can undergo rapid lateral movement or translation at a rate of 5–10 µm/min— an enormous distance on a molecular scale. The recognition protomer of a receptor com- plex therefore need not be permanently associated with an effector molecule, and thus no stoichiometric relationship is required. Instead, the recognition protomer can undergo rapid lateral movement and, when activated to the R state, can engage in what has been dubbed a “collision coupling. Therefore, different recognition sites can activate the same adenylate cyclase molecule at different times through the same mechanism. By the same token, a single recognition site could activate several adenylate cyclase molecules or other effector systems during its active lifetime. Such multiple collision couplings can be seen as the molecular explanation of positive cooperativity and the concept of receptor reserve. However, it is probably true that a recognition site that operates an ion gate is more permanently associated with the ionophore than is the drug or hormone receptor that acts through adenylate cyclase or the phosphatidylinositol system. After the receptor protein is packaged in the Golgi apparatus, various carbohydrates are removed and others are added to the branched oligosaccha- ride “antenna” structures; this process is referred to as “capping. The assembled supramolecular receptor is then inserted into the cell membrane as an intrinsic protein, that is, one that usually spans the width of the lipid bilayer. It can therefore communicate with the extracellular space as well as with the inside of the cell, thus fulfilling its role as a transmembrane signal transducer. Membrane-bound receptors undergo dynamic processes that serve as regulatory mechanisms. This has led to the idea that such receptor regulation is just as important in the overall response of the system as is the response of the target organ (e. There are several categories of regulatory mechanisms, and they differ primarily in the rate of response: some are very fast (milliseconds to seconds), whereas others are much slower and delayed. Upon ligand binding, the receptor may phosphorylate itself on a tyrosine or serine residue, or the ligand-induced conformational change may make the receptor a substrate for a phosphorylase kinase. Sulfhydryl redox reactions, seen in the nicotinic cholinoceptor, result in alteration of relative ligand sensitivities; in the insulin receptor, they lead to affinity changes. Thus covalent modifications of receptors, whether homospecific or heterospecific, lend biochemical significance to the pharmacological terms affinity and intrinsic activity. They can also influence the receptor environment, causing a change in membrane potential or receptor distribution (clustering, patching). A notable example is the effect of Na+ ions on the relative affinity of opiate receptors toward agonists and antagonists. The lateral mobility of the ligand–receptor complex, a phenomenon still not well understood, is further regulated by an alteration in membrane fluidity triggered by the ligand–receptor complex itself. Peptide hormone receptors in particular are known to form clus- ters that are observable microscopically by use of fluorescent receptor probes. Clustering is a necessary but insufficient prerequisite for the pharmacological effect. Ligand bind- ing to clustered receptors is still necessary for cell activation in such instances as insulin receptor-mediated lipolysis in adipocytes (fat cells). As implied earlier, clustering could explain receptor cooperativity in a positive sense, as well as in a negative sense. These pits are apparent in electron micro- graphs as membrane invaginations coated on the inner (cytoplasmic) side with a web of the protein clathrine. It has been suggested that certain receptor proteins have structural domains that allow them to react with coated pits. Perhaps the most important role of internalization is the removal of receptors from the plasma membrane, the down-regulation of a receptor population. Cellular function may be conceptualized into three very broad categories of activity: 1. Transmitting information from one cell to an adjacent cell (via voltage-gated and ligand-gated ion channels).